IL-12 and IL-18 induce interferon-γ production and de novo CD2 expression in porcine γδ T cells

Sedlak, Corinna; Patzl, Martina; Saalmüller, Armin; Gerner, Wilhelm

doi:10.1016/j.dci.2014.07.007

Cited by 30 publications

(20 citation statements)

References 34 publications

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“…For CD2 it was shown that already in the thymus two different lineages of γδ T cells can be identified by this marker [36]. For CD8α and CD27 published data suggest that within CD2 + γδ T cells a CD8α + CD27 − phenotype is related to a late stage of differentiation [35]. Hence, we analysed expression of CD2, CD8α and CD27 in γδ T cells also in this study (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…In lymph nodes, percentage of this population was significantly decreased in E. coli O157:H7 infected animals compared to animals infected with E.coli O104:H4 (p = 0.011). γδ T cells are another prominent T cell subpopulation in the blood [34] and secondary lymphatic organs of pigs [35]. For absolute numbers of γδ T cells in blood, a substantial variation among different piglets was found but without an obvious link to E. coli infection (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7

et al. 2017

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BackgroundShiga toxin (Stx) producing Escherichia coli (E. coli) (STEC) is the most frequent cause of diarrhoea-positive haemolytic uraemic syndrome (D + HUS) in humans. In 2011, a huge outbreak with an STEC O104:H4 strain in Germany highlighted the limited possibilities for causative treatment of this syndrome. The responsible STEC strain was found to combine Stx production with adherence mechanisms normally found in enteroaggregative E. coli (EAEC). Pathotypes of E. coli evolve and can exhibit different adhesion mechanisms. It has been shown previously that neonatal gnotobiotic piglets are susceptible for infection with STEC, such as STEC O157:H7 as well as for EAEC, which are considered to be the phylogenetic origin of E. coli O104:H4. This study was designed to characterise the host response to infection with the STEC O104:H4 outbreak strain in comparison to an STEC O157:H7 isolate by evaluating clinical parameters (scoring) and markers of organ dysfunction (biochemistry), as well as immunological (flow cytometry, assessment of cytokines/chemokines and acute phase proteins) and histological alterations (light- and electron microscopy) in a gnotobiotic piglet model of haemolytic uraemic syndrome.ResultsWe observed severe clinical symptoms, such as diarrhoea, dehydration and neurological disorders as well as attaching-and-effacing lesions (A/E) in the colon in STEC O157:H7 infected piglets. In contrast, STEC O104:H4 challenged animals exhibited only mild clinical symptoms including diarrhoea and dehydration and HUS-specific/severe histopathological, haematological and biochemical alterations were only inconsistently presented by individual piglets. A specific adherence phenotype of STEC O104:H4 could not be observed. Flow cytometric analyses of lymphocytes derived from infected animals revealed an increase of natural killer cells (NK cells) during the course of infection revealing a potential role of this subset in the anti-bacterial activity in STEC disease.ConclusionsUnexpectedly, E. coli O104:H4 infection caused only mild symptoms and minor changes in histology and blood parameters in piglets. Outcome of the infection trial does not reflect E. coli O104:H4 associated human disease as observed during the outbreak in 2011. The potential role of cells of the innate immune system for STEC related disease pathogenesis should be further elucidated.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7

et al. 2017

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“…The lymphocyte preparations in the current study were only partially purified, with no attempts to phenotypic characterization of the cells. However, γδ T cells that can produce both IL-17 and IFN-γ reach high numbers in the porcine circulation [35, 36] that may have contributed to the relative increase in IL-17 and IFN-γ transcription in lymphocytes. IL-12 and IL-18 act synergistically on the IFN-γ production by porcine T cells [35] and IL-12p40 transcripts were detected in lymphocytes cultured in the presence of Matrix-M.…”

Section: Discussionmentioning

confidence: 99%

“…However, γδ T cells that can produce both IL-17 and IFN-γ reach high numbers in the porcine circulation [35, 36] that may have contributed to the relative increase in IL-17 and IFN-γ transcription in lymphocytes. IL-12 and IL-18 act synergistically on the IFN-γ production by porcine T cells [35] and IL-12p40 transcripts were detected in lymphocytes cultured in the presence of Matrix-M. Thus, both the period of exposure to Matrix-M and the total culture time as well as the cell composition appears important for the induction of cytokine gene expression by Matrix-M in vitro.…”

Section: Discussionmentioning

confidence: 99%

Innate immune responses induced by the saponin adjuvant Matrix-M in specific pathogen free pigs

Ahlberg

Hjertner

Wallgren

et al. 2017

Vet Res

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Saponin-based adjuvants have been widely used to enhance humoral and cellular immune responses in many species, but their mode of action is not fully understood. A characterization of the porcine transcriptional response to Matrix-M was performed in vitro using lymphocytes, monocytes or monocyte-derived dendritic cells (MoDCs) and in vivo. The effect of Matrix-M was also evaluated in specific pathogen free (SPF) pigs exposed to conventionally reared pigs. The pro-inflammatory cytokine genes IL1B and CXCL8 were up-regulated in monocytes and lymphocytes after Matrix-M exposure. Matrix-M also induced IL12B, IL17A and IFNG in lymphocytes and IFN-α gene expression in MoDCs. Several genes were indicated as up-regulated by Matrix-M in blood 18 h after injection, of which the genes for IFN-α and TLR2 could be statistically confirmed. Respiratory disease developed in all SPF pigs mixed with conventional pigs within 1–3 days. Two out of four SPF pigs injected with saline prior to contact exposure displayed systemic symptoms that was not recorded for the four pigs administered Matrix-M. Granulocyte counts, serum amyloid A levels and transcription of IL18 and TLR2 coincided with disease progression in the pigs. These results support further evaluation of Matrix-M as a possible enhancer of innate immune responses during critical moments in pig management.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-017-0437-2) contains supplementary material, which is available to authorized users.

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“…Strikingly, physiologically, both cytokines derive from myeloid cells thus innate immune cells. While TCR or NK-receptor stimulation in the presence of IL-12 and IL-18 promotes effector functions such as cytotoxicity and IFN-γ expression, and enhances the clonal expansion of Vγ9Vδ2 T cells [16][17][18][19], a synergistic effect for IL-12 and IL-18 in a TCR-independent production of IFN-γ has been demonstrated for γδ T cells lately [20][21][22]. In an effort to dissect potentially detrimental suppressive activity induced via supraphysiologic pharmacological TCR triggering from anti-tumoral behavior, we hypothesized that this capacity of γδ T cells for TCR-independent activation, namely bypassing the TCR via cytokines, might be an option to generate physiologically activated Vγ9Vδ2 γδ T cells in reasonable numbers for anti-tumoral immunotherapy [20].…”

Section: Introductionmentioning

confidence: 99%

In the Absence of a TCR Signal IL-2/IL-12/18-Stimulated γδ T Cells Demonstrate Potent Anti-Tumoral Function Through Direct Killing and Senescence Induction in Cancer Cells

Schilbach

Welker

Krickeberg

et al. 2020

Cancers

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Abundant IFN-γ secretion, potent cytotoxicity, and major histocompatibility complex-independent targeting of a large spectrum of tumors make γδ T cells attractive candidates for cancer immunotherapy. Upon tumor recognition through the T-cell receptor (TCR), NK-receptors, or NKG2D, γδ T cells generate the pro-inflammatory cytokines TNF-α and IFN-γ, or granzymes and perforin that mediate cellular apoptosis. Despite these favorable potentials, most clinical trials testing the adoptive transfer of pharmacologically TCR-targeted and expanded γδ T cells resulted in a limited response. Recently, the TCR-independent activation of γδ T cells was identified. However, the modulation of γδ T cell’s effector functions solely by cytokines remains to be elucidated. In the present study, we systematically analyzed the impact of IL-2, IL-12, and IL-18 in parallel with TCR stimulation on proliferation, cytokine production, and anti-tumor activity of γδ T cells. Our results demonstrate that IL-12 and IL-18, when combined, constitute the most potent stimulus to enhance anti-tumor activity and induce proliferation and IFN-γ production by γδ T cells in the absence of TCR signaling. Intriguingly, stimulation with IL-12 and IL-18 without TCR stimulus induces a comparable degree of anti-tumor activity in γδ T cells to TCR crosslinking by killing tumor cells and driving cancer cells into senescence. These findings approve the use of IL-12/IL-18-stimulated γδ T cells for adoptive cell therapy to boost anti-tumor activity by γδ T cells.

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IL-12 and IL-18 induce interferon-γ production and de novo CD2 expression in porcine γδ T cells

Cited by 30 publications

References 34 publications

Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7

Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7

Innate immune responses induced by the saponin adjuvant Matrix-M in specific pathogen free pigs

In the Absence of a TCR Signal IL-2/IL-12/18-Stimulated γδ T Cells Demonstrate Potent Anti-Tumoral Function Through Direct Killing and Senescence Induction in Cancer Cells

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